Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction: Comparison at Acute Event and One-Year Follow-Up
MicroRNAs (miRNA) are major regulators of intercellular communication and key players in the pathophysiology of cardiovascular disease. This study aimed to determine the miRNA fingerprint in a cohort of 53 patients with acute myocardial infarction (AMI) with non-ST-segment elevation (NSTEMI) relativ...
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MDPI AG
2022-06-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/11/1823 |
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| author | Ana Mompeón Daniel Pérez-Cremades Ana Belén Paes Juan Sanchis Luis Ortega-Paz Rut Andrea Salvatore Brugaletta Manel Sabate Susana Novella Ana Paula Dantas Carlos Hermenegildo |
| author_facet | Ana Mompeón Daniel Pérez-Cremades Ana Belén Paes Juan Sanchis Luis Ortega-Paz Rut Andrea Salvatore Brugaletta Manel Sabate Susana Novella Ana Paula Dantas Carlos Hermenegildo |
| author_sort | Ana Mompeón |
| collection | DOAJ |
| description | MicroRNAs (miRNA) are major regulators of intercellular communication and key players in the pathophysiology of cardiovascular disease. This study aimed to determine the miRNA fingerprint in a cohort of 53 patients with acute myocardial infarction (AMI) with non-ST-segment elevation (NSTEMI) relative to miRNA expression in healthy controls (<i>n</i> = 51). miRNA expression was initially profiled by miRNA array in the serum of patients undergoing cardiac catheterization during NSTEMI (<i>n</i> = 8) and 1 year past the event (follow-up, <i>n</i> = 8) and validated in the entire cohort. In total, 58 miRNAs were differentially expressed during AMI (<i>p</i> < 0.05), while 36 were modified at follow-up (Fisher’s exact test: <i>p</i> = 0.0138). Enrichment analyses revealed differential regulation of biological processes by miRNA at each specific time point (AMI vs. follow-up). During AMI, the miRNA profile was associated mainly with processes involved in vascular development. However, 1 year after AMI, changes in miRNA expression were partially related to the regulation of cardiac tissue morphogenesis. Linear correlation analysis of miRNA with serum levels of cytokines and chemokines revealed that let-7g-5p, let-7e-5p, and miR-26a-5p expression was inversely associated with serum levels of pro-inflammatory cytokines TNF-α, and the chemokines MCP-3 and MDC. Transient transfection of human endothelial cells (HUVEC) with let-7e-5p inhibitor or mimic demonstrated a key role for this miRNA in endothelial function regulation in terms of cell adhesion and angiogenesis capacity. HUVEC transfected with let-7e-5p mimic showed a 20% increase in adhesion capacity, whereas transfection with let-7e-5p inhibitor increased the number of tube-like structures. This study pinpoints circulating miRNA expression fingerprint in NSTEMI patients, specific to the acute event and changes at 1-year follow-up. Additionally, given its involvement in modulating endothelial cell function and vascularization, altered let-7e-5p expression may constitute a therapeutic biomarker and target for ischemic heart disease. |
| first_indexed | 2024-03-10T01:24:47Z |
| format | Article |
| id | doaj.art-5d61bbf9f9b04be98ab21cbfe0450ab2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:24:47Z |
| publishDate | 2022-06-01 |
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| series | Cells |
| spelling | doaj.art-5d61bbf9f9b04be98ab21cbfe0450ab22023-11-23T13:53:21ZengMDPI AGCells2073-44092022-06-011111182310.3390/cells11111823Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction: Comparison at Acute Event and One-Year Follow-UpAna Mompeón0Daniel Pérez-Cremades1Ana Belén Paes2Juan Sanchis3Luis Ortega-Paz4Rut Andrea5Salvatore Brugaletta6Manel Sabate7Susana Novella8Ana Paula Dantas9Carlos Hermenegildo10Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, INCLIVA Biomedical Research Institute, Avda. Blasco Ibáñez, 15, 46010 Valencia, SpainDepartment of Physiology, Faculty of Medicine and Dentistry, University of Valencia, INCLIVA Biomedical Research Institute, Avda. Blasco Ibáñez, 15, 46010 Valencia, SpainDepartment of Physiology, Faculty of Medicine and Dentistry, University of Valencia, INCLIVA Biomedical Research Institute, Avda. Blasco Ibáñez, 15, 46010 Valencia, SpainCardiology Division, Hospital Clínico Universitario de Valencia (HCUV), INCLIVA Biomedical Research Institute, University of Valencia, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Avda. Blasco Ibáñez, 17, 46010 Valencia, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Carrer del Rosselló, 149, 08036 Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Carrer del Rosselló, 149, 08036 Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Carrer del Rosselló, 149, 08036 Barcelona, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Carrer del Rosselló, 149, 08036 Barcelona, SpainDepartment of Physiology, Faculty of Medicine and Dentistry, University of Valencia, INCLIVA Biomedical Research Institute, Avda. Blasco Ibáñez, 15, 46010 Valencia, SpainInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Carrer del Rosselló, 149, 08036 Barcelona, SpainDepartment of Physiology, Faculty of Medicine and Dentistry, University of Valencia, INCLIVA Biomedical Research Institute, Avda. Blasco Ibáñez, 15, 46010 Valencia, SpainMicroRNAs (miRNA) are major regulators of intercellular communication and key players in the pathophysiology of cardiovascular disease. This study aimed to determine the miRNA fingerprint in a cohort of 53 patients with acute myocardial infarction (AMI) with non-ST-segment elevation (NSTEMI) relative to miRNA expression in healthy controls (<i>n</i> = 51). miRNA expression was initially profiled by miRNA array in the serum of patients undergoing cardiac catheterization during NSTEMI (<i>n</i> = 8) and 1 year past the event (follow-up, <i>n</i> = 8) and validated in the entire cohort. In total, 58 miRNAs were differentially expressed during AMI (<i>p</i> < 0.05), while 36 were modified at follow-up (Fisher’s exact test: <i>p</i> = 0.0138). Enrichment analyses revealed differential regulation of biological processes by miRNA at each specific time point (AMI vs. follow-up). During AMI, the miRNA profile was associated mainly with processes involved in vascular development. However, 1 year after AMI, changes in miRNA expression were partially related to the regulation of cardiac tissue morphogenesis. Linear correlation analysis of miRNA with serum levels of cytokines and chemokines revealed that let-7g-5p, let-7e-5p, and miR-26a-5p expression was inversely associated with serum levels of pro-inflammatory cytokines TNF-α, and the chemokines MCP-3 and MDC. Transient transfection of human endothelial cells (HUVEC) with let-7e-5p inhibitor or mimic demonstrated a key role for this miRNA in endothelial function regulation in terms of cell adhesion and angiogenesis capacity. HUVEC transfected with let-7e-5p mimic showed a 20% increase in adhesion capacity, whereas transfection with let-7e-5p inhibitor increased the number of tube-like structures. This study pinpoints circulating miRNA expression fingerprint in NSTEMI patients, specific to the acute event and changes at 1-year follow-up. Additionally, given its involvement in modulating endothelial cell function and vascularization, altered let-7e-5p expression may constitute a therapeutic biomarker and target for ischemic heart disease.https://www.mdpi.com/2073-4409/11/11/1823microRNA profileserum biomarkermyocardial infarctionendothelial celllet-7eangiogenesis |
| spellingShingle | Ana Mompeón Daniel Pérez-Cremades Ana Belén Paes Juan Sanchis Luis Ortega-Paz Rut Andrea Salvatore Brugaletta Manel Sabate Susana Novella Ana Paula Dantas Carlos Hermenegildo Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction: Comparison at Acute Event and One-Year Follow-Up Cells microRNA profile serum biomarker myocardial infarction endothelial cell let-7e angiogenesis |
| title | Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction: Comparison at Acute Event and One-Year Follow-Up |
| title_full | Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction: Comparison at Acute Event and One-Year Follow-Up |
| title_fullStr | Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction: Comparison at Acute Event and One-Year Follow-Up |
| title_full_unstemmed | Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction: Comparison at Acute Event and One-Year Follow-Up |
| title_short | Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction: Comparison at Acute Event and One-Year Follow-Up |
| title_sort | circulating mirna fingerprint and endothelial function in myocardial infarction comparison at acute event and one year follow up |
| topic | microRNA profile serum biomarker myocardial infarction endothelial cell let-7e angiogenesis |
| url | https://www.mdpi.com/2073-4409/11/11/1823 |
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